Department of Cardiology, Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Taoyuan City 333, Taiwan; Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 350, Taiwan.
Department of General Surgery, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
Obes Res Clin Pract. 2020 May-Jun;14(3):257-263. doi: 10.1016/j.orcp.2020.05.002. Epub 2020 Jun 3.
The FTO (fat mass- and obesity-associated) gene variant is an established obesity-susceptibility locus. FTO protein is a nucleic acid demethylase and FTO genetic variants form long-range functional connections with IRX3, which regulates fat mass and metabolism in humans. From our previous results, we found FTO regulates the metabolism of triglyceride in adipocytes through demethylating Angptl4 (angiopoietin-like protein 4) mRNA in mice. We hypothesized that the FTO genetic variants regulate ANGPTL4 abundances in human adipose tissues and affect the outcome after bariatric surgery.
We recruited 188 obesity subjects with body mass indices (BMI)>35kg/m and 102 non-obese subjects with BMI<30kg/m from the OCEAN registry between 2011 and 2014. The distribution of FTO variants rs9939609 among participates was 73.79% TT, 23.79% AT, and 2.41% AA. The subjects with FTO variants AA or AT were correlated with higher BMI than those with FTO variants TT. The serum ANGPTL4 levels were significantly higher in obese subjects and positively correlated with the presence of FTO AA or AT haplotype. Of these participates, 84 obese subjects underwent bariatric surgery and adipose Angptl4 expressions were analyzed. The adipose Angptl4 mRNA levels and protein abundances were correlated with FTO AA or AT haplotype. The magnitude of excess body weight reduction 2 years after bariatric surgery was correlated with the adipose ANGPTL4 protein levels.
Adipose ANGPTL4 abundances were affected by the presence of FTO obesity risk haplotype and correlated with excess weight loss percentage after bariatric surgery. These data signify the critical role of FTO variants and adipose ANGPTL4 in fatty acid metabolism and bariatric outcomes in humans.
FTO（肥胖相关的脂肪量和肥胖）基因变异是一个已确定的肥胖易感性基因座。FTO 蛋白是一种核酸去甲基酶，FTO 基因变异与 IRX3 形成长程功能连接，IRX3 调节人类的脂肪量和新陈代谢。根据我们之前的研究结果，我们发现 FTO 通过在小鼠中去甲基化 Angptl4（血管生成素样蛋白 4）mRNA 来调节脂肪细胞中甘油三酯的代谢。我们假设 FTO 基因变异调节人类脂肪组织中 ANGPTL4 的丰度，并影响减肥手术后的结果。
我们从 2011 年至 2014 年的 OCEAN 登记处招募了 188 名 BMI>35kg/m 的肥胖患者和 102 名 BMI<30kg/m 的非肥胖患者。参与者中 FTO 变异 rs9939609 的分布为 73.79%TT、23.79%AT 和 2.41%AA。与 FTO 变异 TT 相比，FTO 变异 AA 或 AT 的个体与更高的 BMI 相关。肥胖患者的血清 ANGPTL4 水平显著升高，并与 FTO AA 或 AT 单倍型的存在呈正相关。在这些患者中，84 名肥胖患者接受了减肥手术，并分析了脂肪组织 Angptl4 的表达。脂肪组织 Angptl4 mRNA 水平和蛋白丰度与 FTO AA 或 AT 单倍型相关。减肥手术后 2 年内多余体重减轻的幅度与脂肪组织 ANGPTL4 蛋白水平相关。
脂肪组织 ANGPTL4 的丰度受 FTO 肥胖风险单倍型的影响，并与减肥手术后多余体重减轻的百分比相关。这些数据表明 FTO 变异和脂肪组织 ANGPTL4 在人类脂肪酸代谢和减肥结果中具有关键作用。
